The central inflammatory regulator IκBζ: induction, regulation and physiological functions

Abstract

IκBζ (encoded by NFKBIZ) is the most recently identified IkappaB family protein. As an atypical member of the IkappaB protein family, NFKBIZ has been the focus of recent studies because of its role in inflammation. Specifically, it is a key gene in the regulation of a variety of inflammatory factors in the NF-KB pathway, thereby affecting the progression of related diseases. In recent years, investigations into NFKBIZ have led to greater understanding of this gene. In this review, we summarize the induction of NFKBIZ and then elucidate its transcription, translation, molecular mechanism and physiological function. Finally, the roles played by NFKBIZ in psoriasis, cancer, kidney injury, autoimmune diseases and other diseases are described. NFKBIZ functions are universal and bidirectional, and therefore, this gene may exert a great influence on the regulation of inflammation and inflammation-related diseases.

Pulmonary maternal immune activation does not cross the placenta but leads to fetal metabolic adaptation

“…The transcription factor STAT3 regulates activation of Jak/STAT/IL-6-pathway targets while SOCS2- and SOCS3 inhibit STAT3 and thereby IL-6-induced inflammation 46 , 47 . Nfkbiz can also be induced by STAT3 and inhibits pro-inflammatory signaling by NFKB and TNF 48 , 49 . The gene expression of Junb and Fos , regulatory targets of IL-6-signaling 50 , were also upregulated in the placenta at 2–12 h. Thus, while mRNAs for IL6RA and IL6ST proteins that are necessary for inducing IL-6 signaling had higher expression levels in decidua than placenta regardless of exposure, the genes of the key IL-6 pathway inhibitors Socs2 and Socs3 were only upregulated in the placenta following LPS treatment.…”

Exploring the Health Benefits of Boletus aereus Polysaccharides: Extraction, Structural Characterization, and Antiproliferative Properties against Non-Hodgkin’s Lymphomas (NHLs)

“…For example, increased expression of CXCL9 and CXCL11 suggests enhanced recruitment of immune cells . NFKBIZ is an important regulator in the NF-κB signaling pathway and is involved in the activation of immune pathways that regulate inflammation cell survival . Genes such as CSF2 and PRTN3 may also play a regulatory role in the immune system, participating in some aspects of the host defense mechanisms.…”

“…44 NFKBIZ is an important regulator in the NF-κB signaling pathway and is involved in the activation of immune pathways that regulate inflammation cell survival. 45 Genes such as CSF2 46 and PRTN3 47 may also play a regulatory role in the immune system, participating in some aspects of the host defense mechanisms. Therefore, BAPN-1 may play a positive role in enhancing immune activity while exerting its antitumor effects.…”

Precision Immuno-Chemical Biology: Toward Decoding Spatiotemporal Signaling Activities of Reactive Immunometabolites

“…ATF3-IκBζ axis regulates cytokine production and is implicated in mitochondrial-stress response [47] (Figure 4d). Dysregulation of ATF3-IκBζ-pathway leads to imbalanced immune responses, such as in autoimmune diseases, cancer, and infections, by either promoting excessive inflammation or failing to adequately manage pathogenic threats [48]. An inference of itaconate's ability to modulate ATF3-IκBζ-axis is made using dimethyl itaconate [47] (DI, Figure 4a, another putative mimic of itaconate of increased cell-permeability, and strongly-elevated reactivity; subsequent studies implicate its metabolically-defunct behaviors [49]).…”